Development of ZEPATIER®
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ZEPATIER® (MK-5172A; elbasvir and grazoprevir, Merck & Co., Inc.) is a fixed-dose combination treatment for individuals with chronic hepatitis C virus (HCV) infection. This novel direct-acting antiviral (DAA) regimen combines elbasvir, a selective inhibitor of the HCV nonstructural protein 5A, and grazoprevir, a reversible competitive inhibitor of the HCV nonstructural protein 3/4A protease. After extensive preclinical testing and evaluation of safety and pharmacokinetics (PK) in healthy volunteers, the efficacy of these agents was evaluated in a systematic and comprehensive clinical development program culminating in phase 3 clinical trials in a broad population of participants with HCV infection, including treatment-naive and treatment-experienced participants, those with chronic kidney disease or inherited blood disorders, and those receiving opioid agonist therapy. These studies led to the approval of the elbasvir/grazoprevir combination therapy for the treatment of people with HCV genotype 1 or genotype 4 infection in the United States, Europe, Canada, and many other countries worldwide.
KeywordsClinical trial Elbasvir Grazoprevir, ZEPATIER Hepatitis C Treatment
We extend our gratitude to the participants, their families, investigators, and site personnel who participated in the elbasvir/grazoprevir clinical trials. Medical writing and editorial assistance were provided by Tim Ibbotson, PhD, of ApotheCom, Yardley, PA, and funded by Merck & Co., Inc., Kenilworth, NJ, USA.
Compliance with Ethical Standards
Funding Funding for the studies described in this book chapter was provided by Merck & Co., Inc., Kenilworth, NJ, USA.
Conflict of Interest Drs Robertson and Barr are employees of, and hold stock in, Merck & Co., Inc., Kenilworth, NJ, USA.
All studies were carried out in accordance with the Declaration of Helsinki, current guidelines on Good Clinical Practices and local ethical and legal requirements. For each study, independent institutional review boards or ethics committees reviewed and approved the protocol and applicable amendments.
In all studies, all participants gave written informed consent.
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